System and method for fractional elution of mother-daughter radionuclides

Abstract

A method and system for eluting an eluate containing a daughter nuclide at a desired activity concentration, obtained from a mother / daughter nuclide mixture, are disclosed. The method comprises contacting an aqueous solution containing the mixture of the mother and daughter nuclide with separation particles, wherein the daughter nuclide binds to the separation particles and the mother nuclide does not. The contact is maintained for a time until the unbound daughter nuclide binds to the separation particles. The unbound mother nuclide is separated from the separation particles bound to the daughter nuclide using a washing solution. A first fraction of the bound daughter nuclide is stripped from the separation particles using a certain volume of stripping solution to obtain an aqueous eluate having the desired daughter nuclide activity. A residual aqueous solution containing a second fraction of the desired daughter nuclide, still present in the aqueous solution, is retained.

Description

[Technical Field]

[0001] Cross-reference of related applications This application claims priority on the filing date of U.S. Provisional Application No. 63 / 449,185, entitled "System and Method for Fractional Elution of Mother-Daughter Radionuclides," filed on 1 March 2023, the entire contents of which are incorporated herein by reference as being contained herein in full. Technical field This invention generally relates to the generation and separation of radionuclides for medical purposes. More specifically, the invention aims to provide a method for separating and eluting a parent nuclide and a desired daughter nuclide, which provides improved accuracy in the desired daughter nuclide activity in the collected daughter nuclide eluate compared to using multiple separate elutions. The intended invention can also extend the useful life of a radioactive source because it allows the activity from multiple sources to be utilized in the same liquid volume. [Background technology]

[0002] The use of radionuclides in treatment and diagnosis has increased in recent years, and the need for radionuclides has grown to the point where it exceeds the capacity to rapidly and cost-effectively produce the required isotopes. Consequently, patients and potential patients are left without adequate diagnosis or treatment.

[0003] Examples of radionuclides in demand include rhenium-188 (Re188), a beta-emitting radionuclide with a half-life of approximately 17 days, used in radiopharmaceuticals for the diagnosis and treatment of malignant tumors, bone metastases, and rheumatoid arthritis. Gallium-68 (Ga68), with a half-life of approximately 68 minutes, emits positrons and is used in positron emission tomography (PET) scans. Some PET / CT combined scanners also perform CT (computed tomography) scans in the same session, and then synthesize the images. Technetium-99m (Tc99m), with a half-life of approximately 6 hours, is the most commonly used medical radioisotope in the world, used in tens of millions of medical diagnostic procedures annually in oncology, neurology, and cardiology. Actinium-225 (Ac225) is primarily used in cancer treatment. It has a half-life of approximately 10 days and is an alpha-emitting atom, emitting four alpha particles per initially present Ac225 atom. Medically, it is used in targeted alpha-emitting therapy (TAT) for the treatment of prostate cancer, brain tumors, and neuroendocrine cancers. Bismuth-213 (Bi213) is another alpha-emitting candidate whose application in cancer treatment has been proposed. Each of the isotopes listed above is a radioactive decay product of a parent isotope, which is referred to as the "parent isotope" in this specification, and the listed decay product isotopes are referred to as "daughter isotopes." Therefore, Re188 is a daughter of the parent isotope tungsten-188 (W188), Ga68 is a daughter of germanium-68 (Ge68), Tc99m is a daughter of molybdenum-99 (Mo99), the parent of Ac225 is radium-225 (Ra225), and Bi213 is a daughter of Ac225. With the exception of uranium, it should be understood that each parent isotope is a daughter of a parent isotope with a higher atomic weight. However, as used herein, the isotope used as the immediately preceding starting material is referred to as the parent isotope, and the desired product isotope is referred to as the daughter isotope. Thus, for example, Tc99m is a daughter of molybdenum-99 (Mo99). Both can coexist in the same solution and can be separated from each other before the medical use of Tc99m.

[0004] As an example of a single decay pattern, Bi213 can be obtained by selectively isolating Ac225 from thorium-229 (Th229) containing trace amounts of thorium-228 (Th228) contaminants. In a more complex decay pattern, radium-226, the longest-lived form of radium, can be irradiated with neutrons to produce radium-225 (Ra225) with a half-life of approximately 15 days, which in turn produces Ac225 as its daughter. To obtain Ac225 in a usable form, it must be separated from the potentially untransformed Ra226, the undecayed Ra225, and the possible decay products from Ac225. In this situation, Ac225, the material desired for use, is the daughter nuclide, and the preceding starting material, Ra225, is called the mother isotope. Ra225 is also called the stepdaughter of Ra226 because it is a transmutation product rather than a spontaneous decay product. Ra225 is also the mother of Ac225. However, when Ra226 is the starting material and Ac225 is the desired product, they are called the mother and step-granddaughter, respectively.

[0005] Most medically useful radionuclides are produced by artificially irradiating their parent isotopes using physically large and expensive high-energy nuclear devices, such as cyclotrons, synchrotrons, electron beam devices, or similar equipment, which are generally not located within or near medical treatment or diagnostic centers. Therefore, the artificially produced parent, daughter, or other parent nuclide must be transported. Such transport by ship, rail, public road, and / or aircraft is typically carried out under the jurisdiction and regulations of government agencies.

[0006] In the United States, these transport regulations are stipulated in 49, Sub-Part B, Chapter I, Sub-Part C of the Code of Federal Regulations. In summary, transport regulations become significantly stricter when the activity of cargo such as Mo99 / Tc99 exceeds 19Ci. As a result of these regulations, the total radioactivity of the transported radionuclides is limited, which may lead to receiving medical institutions using isotopic concentrations lower than what would otherwise be desirable. Another limiting factor in activity at the point of use is the degradation of the supply source (mother and daughter) over time. For example, the production of the Mo99 supply source for Tc99m formation is complex, so a fresh supply of Mo99 is not available every day. In the separation method primarily intended here, a solution of the parent nuclide is eluted through a chromatography column (primary separation column, PSC) specific to the desired daughter nuclide. The daughter nuclide is retained in the PSC, while the parent passes through unretained. Next, a small volume of rinse solution is typically passed through the PSC to ensure nearly complete recovery of the parent nuclide. The solution of the parent nuclide is then stored for the generation and storage of the desired daughter and for future processing. The daughter nuclide is stripped from the PSC, and this stripping solution is often passed through a second column (guard column) specific to the parent nuclide. The guard column provides additional decontamination of the parent nuclide from the daughter product. See McAlister and Horwitz, "Automated two column generator systems for medical radionuclides", Applied Radiation and Isotopes 67:1985-1991 (2009).

[0007] Therefore, there is a need for inexpensive and rapid means for medical professionals to increase the desired amount of radioactivity available in a safe, shielded environment. The invention described below is considered to offer one solution to the need for improved, inexpensive, rapid, and useful enhancement of useful radioactivity obtained from a regulations-compliant portable radioactive source. Furthermore, fractional elution can be useful in nuclear pharmaceuticals during production operations, as it allows the residual eluate to be retained for subsequent operations by capturing and eluting only a portion of the source material. Moreover, various activity concentrations and activity levels may be required depending on the application of the parent nuclide, the desired nuclide, and / or product. Therefore, there is a need for a method and system that can efficiently generate a wide range of daughter nuclide activity concentrations and / or activity levels. [Overview of the Initiative]

[0008] In a first embodiment, the present invention envisions a method and system for improving the elution efficiency from a column of separation particles that bind daughter nuclides under one elution condition but do not bind the parent nuclide, and release the daughter nuclides when eluted under different elution conditions, thereby providing a broader range of activity concentrations and activity levels of desired daughter nuclides in the eluted composition. This type of elution is referred to herein as “fractionated elution” or “partial elution.” The improvement here lies in capturing and eluting only the desired daughter nuclides in fractional amounts.

[0009] Therefore, the source material solution still contains the desired daughter nuclide in fractional amounts. By eluting only the fraction of the source material solution, the activity of the non-eluting portion of the source material solution can be preserved for further elution, thereby increasing the efficiency of subsequent elution. Furthermore, it has been found that by using fractional elution, a wide range of daughter nuclide activity concentrations and activity levels can be achieved by adjusting the fraction of the source material being eluted.

[0010] Accordingly, in the first embodiment, the method includes the steps of: contacting separation particles with an aqueous source material solution, the source material solution being a mixture of a parent nuclide and a desired daughter nuclide, wherein the desired daughter nuclide binds to the separation particles and the parent nuclide does not bind to the separation particles, thereby forming a dispersion containing at least water, separation particles, the desired daughter nuclide, separation particles bound to the desired daughter nuclide, and unbound parent nuclide; maintaining the contact for a time sufficient to allow the unbound desired daughter nuclide to bind to the separation particles; separating the unbound parent nuclide from the separation particles bound to the desired daughter nuclide using a washing solution; stripping a first fraction of the bound desired daughter nuclide from the separation particles using a volume of a stripping solution to form an aqueous elution solution having the desired daughter nuclide activity; and retaining a second fraction of the desired daughter nuclide on the separation particles. In a second embodiment, the desired daughter nuclide is TcO4 -1 Tc99m or ReO4 exist as such. -1 This is the Re188, which exists as such.

[0011] In a third embodiment, the separated particles are a plurality of covalently bonded -X-(CH2CH2O) n -CH2CH2R groups (wherein X is O, S, NH, or N-(CH2CH2O) m -R 3 and m is a number having an average value of from zero to about 225, n is a number having an average value of from about 15 to about 225, and R 3 is hydrogen, C1-C2 alkyl, 2-hydroxyethyl, or CH2CH2R, and R - is OH, a C1-C n hydrocarbyl ether having a molecular weight of up to about one tenth of the molecular weight of the -(CH2CH2O) 10 moiety, a carboxylate, a sulfonate, a phosphonate, and a -NR 1 R 2 group selected from the group consisting of, and each of R 1 and R 2 is independently hydrogen, C2-C3 hydroxyalkyl, or C1-C6 alkyl, or -NR 1 R 2 together form a 5- or 6-membered cyclic amine having zero or 1 oxygen atom and zero or 1 additional nitrogen atom in the ring), and the separated particles contain particles having a CH2O percent / particle surface area mm greater than about 8,000 and less than about 1,000,000 2 . In a fourth embodiment, the parent nuclide of the desired daughter nuclide Tc99m is present as MoO4 -2 . In a fifth embodiment, the parent nuclide of the desired daughter nuclide Re188 is present as WO4 -2 . In a sixth embodiment, the desired daughter nuclide is Ac225 which is present as Ac +3 . In a seventh embodiment, the parent nuclide of the desired daughter nuclide Ac225 is present as Ra +2 . In an eighth embodiment, Ra +2 is one or both of Ra225 and Ra226.

[0012] In the ninth embodiment, the separated particles are dispersed on a porous resin or silica carrier and have a structure of formula I: [ka] (In the formula, R 1 , R 2 , R 3 , and R 4 They are either identical or different, and are a hydride or hydrocarbyl group, R 1 +R 2 +R 3 +R 4 The total number of carbon atoms is approximately 14 to 56. It contains a corresponding diglycolamide extractant. In the tenth embodiment, the desired daughter nuclide is Ga +4 This is the Ga68 that exists as such. In the 11th embodiment, the desired daughter nuclide Ga +4 The parent nuclide is Ge +4 It exists as such. In the twelfth embodiment, the separated particles comprise a strongly basic anion exchange resin having quaternary ammonium functional groups bonded to a styrene-divinylbenzene copolymer lattice crosslinked with about 2 to about 12% by mass of divinylbenzene. In the 13th embodiment, the desired daughter nuclide is Bi +3 This is Bi213, which exists as such. In the 14th embodiment, the parent nuclide of the desired daughter nuclide is Ac +3 This is the Ac225 that exists as such.

[0013] In a fifteenth embodiment, an elution system is provided for eluting an eluate containing a desired daughter nuclide having a desired activity concentration of nuclide activity. The elution system includes a first inlet for a conditioning fluid; a second inlet for a stripping fluid; a fluid transfer system fluid-communicating with the first and second inlets; a primary separation cartridge (PSC) bay fluid-communicating with the fluid transfer system; a source container, which may also be called a source farm, fluid-communicating with the fluid transfer system; a recycle accumulator fluid-communicating with the fluid transfer system; and a product bay fluid-communicating with the fluid transfer system.

[0014] In a sixteenth embodiment, the fluid transfer system includes an inlet manifold including an inlet valve configured to direct the direction of fluid flow through an inlet manifold; a pump manifold located downstream of the inlet manifold and in fluid communication with the inlet manifold, including a pump valve configured to direct the direction of fluid flow through the pump manifold; a pump located downstream of the inlet manifold and in fluid communication with the pump manifold; a PSC manifold located downstream of the pump manifold and in fluid communication with the pump manifold, including a PSC valve configured to direct the direction of fluid flow through the PSC manifold; and an outlet manifold located downstream of the PSC manifold and in fluid communication with the PSC manifold, including an outlet valve configured to direct the direction of fluid flow through the outlet manifold. In the 17th embodiment, the PSC bay includes one or more isolation columns. In aspect 18, the source container includes one or more source containers and one or more transfer containers. In the 19th embodiment, the recycling accumulator includes one or more recycling containers designed to collect one or more fluids that have passed through the elution system. In the 20th embodiment, the product bay includes a product container. In the 21st embodiment, the product bay includes a guard column upstream of the product vessel. In the 22nd embodiment, the elution system includes a stripping solution pump located downstream of the second inlet, in fluid communication with the second inlet, and upstream of the fluid transfer system.

[0015] In a 23rd embodiment, a method for improving the nuclide activity of an aqueous eluate containing a desired daughter nuclide separated from an aqueous composition containing a parent nuclide and a daughter nuclide, comprising: 1) contacting the aqueous composition with a separation medium so that the desired daughter nuclide has a high affinity to the separation medium and binds to the separation medium, while the parent nuclide has a low affinity to the separation medium and does not bind to the separation medium, thereby forming a dispersion containing at least water, a separation medium, a desired daughter nuclide, a separation medium bound to the desired daughter nuclide, and an unbound parent nuclide; 2) maintaining the contact for a time sufficient for the unbound desired daughter nuclide to bind to the separation medium; 3) separating the unbound parent nuclide from the separation medium bound to the desired daughter nuclide formed in step 2) using a washing solution; 4) stripping the bound desired daughter nuclide from the separation medium using a certain volume of stripping solution to form an aqueous eluate; in the method, The improvement includes stripping a first fraction of a desired bound daughter nuclide from the separated particles using a certain volume of stripping solution to form an aqueous elution solution having the desired daughter nuclide activity, thereby retaining a second fraction of the desired daughter nuclide on the separated particles, thereby improving the desired daughter nuclide activity in subsequent elution compared to when the separated particles do not retain a fraction of the desired daughter nuclide. In the 24th embodiment, the desired daughter nuclide is TcO4 -1 Tc99m or ReO4 exist as such. -1 This is the Re188, which exists as such. In the 25th embodiment, the parent nuclide of the desired daughter nuclide Tc99m is Mo4 -2 It exists as such. In the 26th embodiment, the parent nuclide of the desired daughter nuclide Re188 is WO4 -2 It exists as such. In the 27th embodiment, the parent nuclide of the desired daughter nuclide Re186 is present in W186. In the 27th embodiment, the desired daughter nuclide is Ac +3 This is the Ac225 that exists as such. In the 28th embodiment, the parent nuclide of the desired daughter nuclide Ac225 is Ra +2 It exists as such. In the 29th embodiment, Ra +2 This is either Ra225 or Ra226, or both. In the 30th embodiment, the desired daughter nuclide is Ga +4 This is the Ga68 that exists as such. In the 31st embodiment, the desired daughter nuclide Ga +4 The parent nuclide is Ge +4 It exists as such.

[0016] Accordingly, the present invention envisions an improved method for capturing and eluting a fraction of a desired daughter nuclide into an eluted composition from a column of separation particles that binds to a daughter nuclide under one loading condition but does not bind to a parent nuclide, and which releases a daughter nuclide when eluted under different elution conditions, as well as a system for such elution. The advantage of fractional elution is that by adjusting the fractionation of the source material being eluted, a wider range of daughter nuclide activity concentrations and levels can be achieved. Therefore, users can obtain the desired activity concentration and / or level of the daughter nuclide with greater precision.

[0017] Furthermore, since only a fraction or part of the source material is eluted, the daughter nuclide fraction can be retained in the source material. The advantage of retaining the daughter nuclide fraction is that the user can obtain a larger quantity of the daughter nuclide from subsequent elutions. Therefore, fractional elution can provide a more accurate and efficient elution method.

[0018] As used herein, the term "hydrocarbyl" is a concise term for non-aromatic groups, including linear and branched aliphatic and alicyclic groups or radicals, that contain only carbon and hydrogen. Since alicyclic groups are cyclic aliphatic groups, such substituents are considered to be included within the category of aliphatic groups below. Thus, alkyl groups, alkenyl groups, and alkynyl groups are intended, while aromatic hydrocarbons such as phenyl and naphthyl groups, which are strictly speaking hydrocarbyl groups as well, are referred to herein as aryl groups, substituents, subgroups, or radicals, as will be discussed below. [Brief explanation of the drawing]

[0019] [Figure 1] This figure shows an exemplary embodiment of a fluid flow and elution system using a first conditioning step in a fractionation elution method. [Figure 2] This figure shows an exemplary embodiment of a dissolution system using a second loading step in a fractionation dissolution method. [Figure 3] This figure shows an exemplary embodiment of a dissolution system using a third loading step in a fractionation dissolution method. [Figure 4] This figure shows an exemplary embodiment of an elution system using a fourth washing step in a fractionation elution method. [Figure 5] This figure shows an exemplary embodiment of a elution system using a fifth pH adjustment step in a fractionation elution method. [Figure 6] This figure shows an exemplary embodiment of an elution system using a sixth collection step in a fractionation elution method. [Figure 7] This figure shows an exemplary embodiment of an elution system using a seventh conditioning step in a fractionation elution method. [Modes for carrying out the invention]

[0020] While the present invention can be implemented in many different forms, specific embodiments are shown in the drawings and described in detail herein, with the understanding that this disclosure is illustrative of the principles of the invention. The invention is not intended to be limited to any specific illustrated embodiment. Features of the invention disclosed herein in the specification, drawings, and claims may be important to the implementation of the invention in various embodiments, individually or in any desired combination. Features of one embodiment may be used in other embodiments of the invention. The use of the article "a" or "an" is intended to include one or more. The present invention envisions a method for improving the elution efficiency of an eluate containing a desired daughter nuclide, obtained from a solution containing a mixture of a parent nuclide and a desired daughter nuclide, and optionally other nuclides, and providing a wider range of activity concentrations and activity levels, as well as a system for such elution. Elution generally involves contacting an aqueous solution containing a mixture of a parent nuclide and a desired daughter nuclide with separation particles.

[0021] Desired daughter nuclide ion (e.g., Bi +3 Ac +3 , or Ra +2 Atomic ions such as TcO4, or complex ions containing them, for example TcO4 -1 and ReO4 -1 The isotope has a high affinity for the separation medium (binding to or adhering to the separation medium if it is not), and the parent nuclide has a low affinity for the separation medium (not binding to the separation medium), thus forming a dispersion containing at least water, the separation medium, the desired daughter nuclide, the separation medium bound to the desired daughter nuclide, and the unbound parent nuclide. The contact is maintained for a sufficient time for the unbound desired daughter nuclide to bind to the separation particles (loading onto the separation medium). This time is usually relatively short, about 1 to 30 minutes, during which the parent isotope does not bind to the separation particles, while the daughter isotope does. The unbound parent nuclide is separated from the separation particles bound to the desired daughter nuclide formed in the previous step using a washing solution. Loading into the separation medium can be repeated at least once, up to the limit at which the desired daughter nuclide binds to the separation particles to be used. Next, the bound daughter nuclide is stripped from the separation particles using a certain volume of stripping solution to form an aqueous elution solution with improved activity of the desired daughter nuclide.

[0022] Broadly speaking, the parent isotope and, if applicable, other undesirable materials typically pass through the separation medium, while the desired daughter isotope binds to the column. The relative affinity of the ions containing the parent and daughter isotopes to the separation medium is usually measured as a decontamination factor (DF), which can be obtained from the ratio of the dry mass distribution ratio (Dw) of the analyte to the impurities. A Dw value of less than 20 generally means that the separation medium retains very little of the ions.

[0023] The individual separation media within the column used are, under contact conditions, probably about 10 1 It provides the decontamination factor (DF) for a desired daughter nuclide from a parent nuclide impurity present in a greater or greater state. Typical DF values ​​are more commonly around 10 under contact conditions. 2 ~about 10 5 That's all. Approximately 10 10 The DF value is the approximate maximum DF that can be easily determined using a typical radioanalytical experimental apparatus. The decontamination factor, its definition and calculation are discussed in U.S. Patents 5,603,834 and 6,852,296 by Bond et al., column 20, row 55 to column 21, row 26, as well as in some other patents and publications referenced herein. Using the DF value as a reference, the difference between the high affinity and low affinity of the separation medium between the parent nuclide ion and the daughter nuclide ion provides a DF value of approximately 10¹ or greater, preferably approximately 10² to approximately 10⁵ or greater, and a maximum of approximately 10¹⁰. The parent DF value is approximately 0 to approximately 1. Alternatively, the parent nuclide exhibits a Dw value of less than approximately 20 when used with the intended separation medium.

[0024] While the above method is considered general, different parent and daughter nuclides may require different separation particles and solutions for loading, washing, and stripping the desired bound daughter nuclide from the separation particles. Exemplary parent-daughter nuclide pairs include W188 and Re188, Ge68 and Ga68, Mo99 and Tc99m, Th229 and Ac225, Ra225 and Ac225, Ac225 and Bi213, Th227 and Ac227, Ra223, Ra224 and Pb212, Th228 and Ra224, and Sr82 and Rb82. Note that Ra226 is also the grandmother nuclide of Ra225, and Ra225 is the direct mother of Ac225. The proposed methods and systems may utilize one or more separation media. The separation media used for a given separation is, as is well known, governed by the radionuclides being separated. The particles can be extremely diverse in composition, are inert (unresponsive to the media, solution, and temperature used for separation), and are insoluble in separation / recovery aqueous environments, which may be strongly acidic or strongly basic.

[0025] The preferred separation medium is a solid-phase resin of constant size and form, typically bead-shaped (generally spherical), usually existing as particles, but sheets, webs, or fibers of the separation medium can also be used. In a preferred method utilizing separation medium beads, carrier beads containing the separation medium are packed into a column. When a solution is passed through the beads, the solution can flow over, through, or around the beads, and come into close contact with the separation medium. Smaller separation particles, e.g., 200-400 mesh (80-5 μm), are preferred over larger particles, e.g., 80-120 mesh (180-115 μm), due to the larger surface area per gram provided by the smaller particles. In addition, porous materials with smaller pore sizes are preferred. Exemplary separation particles are discussed in the U.S. patent cited below. The separation media intended are typically commercially available solids, porous particles, or resins containing chelating groups or other binding groups that provide affinity to daughter isotopes, allowing the daughter nuclides to interact and adhere, while the mother isotope exhibits a lower affinity, either not adhering as strongly or not at all. The mechanisms by which such media work and the separation results obtained using such media are well understood in the art to a degree sufficient to make these materials commercially viable.

[0026] Therefore, using the separation media discussed, as suggested in the manufacturer's literature, typically yields isotope separation sufficient to meet government standards, making it possible to use the finally separated daughter isotopes in human medicine. Exemplary data on the differences in binding and elution of mother and daughter isotopes can be found in the disclosures of U.S. Patents 5,707,525, 5,603,834, 5,888,397, 6,852,296, 7,157,022, and 7,553,461, as well as in the publications cited herein and those cited herein.

[0027] One type of separation medium comprises particles having a diglycolamide (DGA) extractant dispersed in an inert porous carrier, such as a polymer resin or silica particles. Such a separation medium is intended to contain pre-selected polyvalent metal cations, such as pseudolanthanides (e.g., scandium(III) and yttrium(III)), prelanthanides (lanthanum(III)), lanthanides, preactinides (actinium(III)), or trivalent americium (Am). +3 ), Yttrium (Y +3 ), and ytterbium (Yb 3+ Actinide cations such as ) cations, other cations present in acidic aqueous solutions, such as radium (Ra +2 ) can be separated from the cation. The pre-selected polyvalent metal cations intended other than cadmium typically have a crystalline ionic radius of about 0.8 to about 1.2 in angstroms.

[0028] Exemplary processes for separating Ac225 from radium ions, such as Ra225 and Ra226, are exemplified in U.S. Patents 7,157,022 and 7,553,461 by Horwitz et al., which describe a process for separating Ac225 from radium ions, such as Ra225 and Ra226, using the following formula I dispersed in a porous inert resin or silica carrier. [ka] (In the formula, R 1 , R 2 , R 3 , and R 4 They are either identical or different, and are a hydride or hydrocarbyl group, R 1 +R 2 +R 3 +R 4 The total number of carbon atoms is approximately 14 to 56. The patent claims describe and describe separated particles containing a diglycolamide extractant whose structure corresponds to [the specified particle].

[0029] These resins are available from Eichrom Technologies, Inc. under the collective name "DGA resins." Within a specific molecule, R 1 , R 2 , R 3 , and R 4 Two types of DGA resins with the same properties are available. One is N,N,N',N'-tetra-n-octyl-diglycolamide (DGA resin, commonly used), and the other is N,N,N',N'-tetra-2-ethylhexyldiglycolamide (DGA resin, branched; sometimes TEHDGA resin). Exemplary preferred particles include particularly preferred reactive crosslinked poly(styrene-vinylbenzylhalide) resins (often called Merrifield peptide resins or chloromethylated divinylbenzene crosslinked polystyrene), as well as glass or silica gel (silica-based) materials, crosslinked poly(ethylene glycol)-containing urethane or urea resins, crosslinked dextran and agarose-based materials, and various crosslinked acrylate esters. The separated particles may contain several reactive functional groups, such as benzylhalide groups that can react in an aqueous two-phase forming environment.

[0030] Exemplary separation particles for Mo99 / Tc99m and W188 / Re188 pairs are discussed in U.S. Patents 5,603,834 and 5,888,397 by Rogers et al. These patents disclose and claim the use of separation particles that are inert and insoluble in aqueous salt two-phase formation environments for separation / recovery, which can be highly diverse in composition and can be strongly acidic or strongly basic. Exemplary preferred particles include particularly preferred reactive crosslinked poly(styrene-vinylbenzylhalide) resins (often called Merrifield peptide resins or chloromethylated divinylbenzene crosslinked polystyrene), as well as glass or silica gel (silica-based) materials, crosslinked poly(ethylene glycol)-containing urethane or urea resins, crosslinked dextran and agarose-based materials, and various crosslinked acrylate esters. The separated particles may contain several reactive functional groups, such as benzylhalide groups that can react in an aqueous two-phase forming environment.

[0031] These separated particles are -X-(CH2CH2O) linked by multiple covalent bonds. n -Contains a CH2CH2R group, where X is O, S, NH, or N-(CH2CH2O) m -R 3 Here, m is a number with an average value between zero and approximately 225, and n is a number with an average value between approximately 15 and approximately 225. 3 is hydrogen, C1-C2 alkyl, 2-hydroxyethyl, or CH2CH2R, where R is - OH, molecular weight is -(CH2CH2O) n The molecular weight of the portion is up to approximately 1 / 10th of C1-C 10 Hydrocarbyl ethers, carboxylates, sulfonates, phosphonates, and -NR 1 R 2 Selected from a group consisting of R 1 and R 2 Each of these is independently hydrogen, a C2-C3 hydroxyalkyl group, or a C1-C6 alkyl group, or -NR 1 R 2Together, they form a 5- or 6-membered cyclic amine having zero or one oxygen atom, or zero or one additional nitrogen atom, within the ring. These separated particles have a CH2O percent / particle surface area mm² of more than approximately 8,000 and less than approximately 1,000,000. 2 It holds.

[0032] Particularly preferred separation particles (mediums) in this group are available under the name ABEC® from Eichrom Technologies, Inc., located at 1955 University Ln, Lisle, IL 60532, USA. These materials and their properties are discussed in Gula and Harvey, "Separation, Concentration, and Immobilization of Technetium and Iodine from Alkaline Supernate Waste," Final Report, March 11, 1998, DE-AC21-97MC33137-43. ABEC® resins and separation using them are also discussed in Bond et al., Ind Eng Chem Res 38(4):1676-1682 (1999) and Bond et al., Ind Eng Chem Res 38(4):1683-1689 (1999).

[0033] An example of a chaotropic anion is a simple anion, such as Br. -1 and I -1 , as well as polyatomic anions, such as TcO4 -1 ReO4 -1 Examples include , or IO3-1. Chaotropic anions can also be complexes of metal cations with halide anions or pseudohalide anions. A particularly useful separation achievable using this separation medium is the parent nuclide 99MoO4 -2 99mTcO4 from an aqueous solution also containing ions -1This is the separation of [the substance]. Further details regarding ABEC® separation media and their use can be found in U.S. Patents 5,603,834, 5,707,525, and 5,888,397. Another method for separating rhenium from tungsten involves capturing tungstic acid in alumina, followed by drying for transport and stripping with aqueous salts. See Argyrou et al., Int J Mol Imaging 2013, Article ID 290750, page 7.

[0034] An exemplary process for separating Ac225 from Th229 is described in U.S. Patent No. 7,087,206 by Bond et al., which discloses the purification of actinium(III) cations, such as Ac225, using a multi-stage column-selective inversion generator, in which Ac225 and its nearest radioactive parent nuclide, radium(II) cation, such as Ra225, are efficiently removed from a solution containing thorium(IV) cations, such as Th229, and the radioactive isotope impurity Th228, preferably by using a first separation medium which preferably contains a strongly acidic sulfonate-containing polymer extractant, such as a cation exchange resin, as will be discussed later.

[0035] The aqueous, preferably acidic, sulfonate solutions of the radioactive parent and daughter are preferably in radioactive equilibrium as ions in the solution before contact with the first separation medium. Examples of anion exchange resins include Bio-Rad® AG® MP-50 macroporous sulfonic acid cation exchange resin, Bio-Rad® 50W-X8 cation exchange resin (which may be supplied in H+ form), Amberlite® IRA-900, IRA-904, and IRA-402 resins, all commercially available from Bio-Rad Laboratories, Inc. in Hercules, CA, and Dowex® 1X2-100, 1X2-400, and 1X4-200 resins, all commercially available from Sigma Chemical Co. in St. Louis, MO.

[0036] Exemplary processes for separating Ac225 from radium ions, such as Ra225 and Ra226, are illustrated in U.S. Patent Nos. 7,157,022 and 7,553,461 to Horwitz et al., which describe and claim separation particles comprising a diglycolamide extractant having a structure corresponding to Formula I.

Chemical formula

[0037] According to U.S. Patent No. 7,728,310 to Fitzimmons et al., aqueous gallium 68 as Ga4Cl4 is separated using an anion exchange resin, such as Bio-Rad AG® 1-X8, analytical grade, 100-200 mesh chloride form, and Ge +4It can be separated from germanium-68 as Cl4. Bio-Rad AG(registered trademark) 1-X8 is said to be a styrene-divinylbenzene copolymer lattice bonded with quaternary ammonium functional groups. The AG(registered trademark) 1-X8 anion exchange resin contains approximately 8% by mass of crosslinks (X8), and similar resins with 2, 4, 10, and 12% by mass of crosslinks are available in multiple mesh sizes from Bio-Rad Laboratories, Inc. in Hercules, CA, USA.

[0038] Exemplary processes for separating Bi213 from radiophilic ions, such as Ac225 and Ra225, are exemplified in U.S. Patent No. 6,852,296 by Bond et al., which describes and claims the purification of Bi213 by a multi-stage column-selective inversion generator. Bond discloses the extraction of Bi213 from a nuclide mixture by adsorbing Bi213 onto a primary separation column containing a polymer coated with particulate material, such as a phosphoryl group-containing extractant (similarly insoluble in water). Particularly preferred separation particles of this group are available under the name UTEVA® from Eichrom Technologies, Inc., U.S., Lisle, IL 60532. The primary separation column is packed, washed with 0.10 M HCl, and stripped with a 0.75 M NaCl solution in 0.50 M (Na+, H+)OAc at pH=4.0 and 25 (±2) °C. The eluate from the primary separation column is directed to pass through a guard column without chemical adjustment. This guard column retains any potentially long-lived Ra225 / 224 or Ac225 contaminants, ensuring high nuclide purity of the Bi213 product.

[0039] In a preferred embodiment, the guard column contains Bio-Rad® AGMP-50 macroporous sulfonic acid cation exchange resin. Bio-Rad® 50W-X8 cation exchange resin may be supplied in H+ form and is commercially available from Bio-Rad Laboratories, Inc. in Hercules, CA, USA. Other useful strongly acidic cation exchange media include Bio-Rad® AGMP-50 and Dowex® 50W series ion exchange resins, as well as Amberlite® IR series ion exchange resins available from Sigma Chemical Co. in St. Louis, MO. Anion exchange resins, such as Bio-Rad® AGMP-1 and Dowex® 1 series anion exchange resins, can also function as separation medium particles. Another particularly useful separation medium, described in U.S. Patent No. 5,110,474 by Horowitz et al., is called "Sr resin" and is available from Eichrom Technologies, Inc. Briefly, Sr resin comprises an inert resin substrate in which a solution of a crown ether extractant dissolved in a liquid diluent is dispersed.

[0040] Liquid diluents are organic compounds having (i) a high boiling point, i.e., about 170°C to about 200°C at a certain atmospheric pressure, (ii) limited solubility in water or insolubility in water, and (iii) being a substance in which crown ethers dissolve. Examples of these diluents include alcohols, ketones, carboxylic acids, and esters. The most preferred alcohol is 1-octanol, but 1-heptanol and 1-decanol are also satisfactory. As for carboxylic acids, in addition to heptanoic acid and hexanoic acid, octanoic acid is preferred. Examples of ketones include 2-hexanone and 4-methyl-2-pentanone, and examples of esters include butyl acetate and pentyl acetate. These resins are discussed more fully in U.S. Patents 5,110,474 and 6,511,630 by Horowitz and Dietz, respectively.

[0041] The macrocyclic polyether can be a dicyclohexanocrown ether, such as dicyclohexano-18-crown-6, dicyclohexano-21-crown-7, or dicyclohexano-24-crown-8. A preferred crown ether has the formula: 4,4'(5')-[(R,R')dicyclohexano]-18-crown-6, where R and R are one or more members selected from the group consisting of linear or branched alkyl groups containing H and 1 to 12 carbon atoms. Examples include methyl, propyl, isobutyl, t-butyl, hexyl, and heptyl. A preferred ether is dicyclohexano-18-crown-6 (DCH 18 C6) and bis-methylcyclohexano-18-crown-6 (DMeCH 18 C6) is one example. The most preferred ether is bis-4,4'(5')-[(di-t-butyl)cyclohexano]-18-crown-6(Dt-BuCH 18 C6)

[0042] The amount of crown ether in the diluent may vary depending on the specific form of the crown ether. For example, the most preferred form is the t-butyl form (Dt-BuCH) at a concentration of about 0.1 to about 0.5 M in the diluent. 18 C6) is satisfactory, with approximately 0.2 M being most preferred. When using the hydrogen form, the concentration can vary in the range of approximately 0.25 to approximately 0.5 M. A preferred Sr resin is a crown ether dissolved in n-octanol (5-20% by mass), such as Dt-BuCH 18 An inert resin substrate is used, which has a coating layer of C6 (20-25% by mass) and a load of 40% by mass of extractant, such as Amberlite® XAD-7 (60-70% by mass). (See Horwitz et al., Solvent Extr. Ion Exch., 10(2):313-316 (1992).)

[0043] Pb resin, a related resin also available from Eichrom Technologies, Inc., has been observed to be useful for the purification and accumulation of Pb212 for the production of Bi212. Pb resin has similar properties to Sr resin, except that a high molecular weight alcohol, i.e., isodecyl alcohol, is used in the production of Pb resin. (See Horwitz et al., Anal. Chim. Acta, 292:263-273 (1994).) It has been observed that stripping from the subsequent 212Bi resin is possible with Pb resin, whereas Pb212 is strongly retained by Sr resin.

[0044] An improved Sr resin, also available from Eichrom Technologies, Inc., offers even greater selectivity. This separation medium is called Super Pb(Sr)® Selective Resin and is dispersed in an inert porous carrier, such as a polymer resin (e.g., Amberchrom®-CG71) or silica particles, containing approximately 5-50% by mass of bis-4,4'(5')[C3-C8-alkylcyclohexano]18-crown-6, e.g., Dt-BuCH, exhibiting a partition coefficient (Dcrown = [crownOrg] / [crown]Aq) greater than approximately 103, and typically about 103-106, between n-octanol and 1M nitric acid. 18 The separation medium contains fluid particles having C6. The separation medium does not contain a diluent, and in particular does not contain a diluent that (i) is insoluble in water or has limited (slight) solubility, or (ii) is capable of dissolving a substantial amount of water present in the Sr resin. See U.S. Patent No. 6,511,603. The preferred washing and stripping solutions used are also selected based on the parent and daughter nuclides and the desired use of the product. Readers should refer to U.S. Patent No. 5,854,968 by Horwitz et al. and U.S. Patent No. 5,863,439 by Dietz et al. for illustrative considerations of this separation medium.

[0045] While a wide range of elution modes and exemplary embodiments have been discussed, the following discussion and Figures 1-7 illustrate preferred embodiments and methods of fractional elution within the elution system 100. The elution system 100 may include one or more inlets or feed ports. As seen in Figures 1-7, the elution system 100 may include a first inlet 110 for the conditioning solution and a second inlet 120 for the stripping solution. The first inlet 110 and the second inlet 120 may each further include pumps. For example, the first inlet 110 may include a stripping solution pump 122. Additional inlets to the elution system 100 may be included in the source container 400. These inlets may supply the fluid transfer system 200 and / or the PSC (Primary Separation Cartridge) bay 300. These components may form a fluid flow control system. These components may then supply the recycle accumulator 500 and / or the product bay 600. The recycling accumulator 500 and / or product bay 600 can serve as the outlet or discharge port for the elution system 100.

[0046] The fluid transfer system 200 can be in fluid communication with the first inlet 110, the second inlet 120, and / or the supply source container 400. Thus, the fluid transfer system 200 may include one or more components for directing the fluid flowing through the fluid transfer system 200, for example, an inlet manifold 210 including an inlet valve 212, a pump 220, a pump manifold 230 including a pump valve 232, a PSC manifold 240 including a PSC valve 242, and an outlet manifold 250 including an outlet valve 252. These components of the fluid transfer system 200 can control the fluid flow through the elution system 100 and the direction of the fluid flow.

[0047] The PSC bay 300 may include one or more columns 310, each containing the ABEC® resin described above. The PSC bay 300 can be in fluid communication with the fluid transfer system 200, and a fluid flow path can be formed between the PSC manifold 240 and the columns 310. The source container 400 provides one or more inlets or inputs to the system and may include one or more supply positions and / or one or more transfer positions. As shown, the source container 400 includes eight source positions 410a to 410h, collectively referred to as source positions 410. The source location 410 may contain source material, such as a liquid solution of a parent nuclide. The source container 400 further includes two transfer locations 420a to 420b, collectively referred to as transfer location 420. Transfer location 420 can be designed to contain the source material solution that has passed through the elution system 100. It should be understood that the source container 400 may include more or fewer source locations 410 and / or transfer locations 420, depending on the embodiment. The source container 400 can be in fluid communication with the fluid transfer system 200, with a fluid path formed between the source location 410 and the inlet manifold 210, and another fluid path formed between the transfer location 420 and the outlet manifold 250.

[0048] The recycling accumulator 500 may include one or more recycling containers for collecting conditioning fluid, residual source material solution, stripping solution, or any other fluid that has passed through the elution system 100. As shown, the recycling accumulator 500 includes six recycling containers 510a to 510f, collectively referred to as recycling container 510. However, the recycling accumulator 500 may include more or fewer recycling containers 510 depending on the embodiment. The recycling accumulator 500 can be in fluid communication with the fluid transfer system 200, forming a fluid path between the outlet manifold 250 and the recycling container 510. The product bay 600 may include a guard column 610 and a product container 620 for collecting product material solutions, such as desired daughter nuclide solutions. In a preferred embodiment, the guard column 610 is a particulate alumina guard column. The product bay 600 can be in fluid communication with the fluid transfer system 200, forming a fluid path between the outlet manifold 250 and the guard column 610. In that case, the product bay 600 may serve as the outlet or discharge port of the elution system 100.

[0049] As shown in Figure 1, in one embodiment of the elution system 100 and method for fractional elution, the first step includes conditioning and preparing the column 310 by flowing a conditioning solution from a first inlet 110 to a fluid transfer system 200 and throughout the column 310 in order to load a source material solution containing a mixture of a parent nuclide and a desired daughter nuclide, and optionally other nuclides, into the column 310. As described above, the elution system 100 may include one or more valves for controlling the flow through the elution system 100.

[0050] Therefore, in one exemplary embodiment of the first valve configuration, the inlet valve 212, pump valve 232, PSC valve 242, and outlet valve 252 can be arranged so that the conditioning fluid enters the fluid transfer system 200 via the inlet manifold 210, passes through the pump 220, through the pump manifold 230 and the PSC manifold 240, through the column 310 of the PSC bay 300, through the PSC manifold 240 again, through the outlet manifold 250, and is discharged to the recycling container 510 of the recycling accumulator 500. The pump 220 may help to provide a desired flow rate through the elution system 100. After conditioning column 310, in the second step shown in Figure 2, fractional amounts of source material solution contained in one or more of the source positions 410 are introduced from the source container 400, loaded into the entire column 310, and collected at the transfer position 420.

[0051] Therefore, in one exemplary embodiment of the second valve configuration, the inlet valve 212, pump valve 232, PSC valve 242, and outlet valve 252 can be arranged such that the source material solution enters the fluid transfer system 200 via the inlet manifold 210, passes through the pump 220, is directed through the pump manifold 230 and PSC manifold 240, moves through the column 310 of the PSC bay 300, passes through the PSC manifold 240 again, passes through the outlet manifold 250, and exits the fluid transfer system 200 to the transfer position 420.

[0052] The source material solution can be loaded from the top to the bottom of column 310, or from the bottom to the top of column 310, depending on the orientation of the PSC valve 242. Furthermore, the software can be used to track the fraction of the eluted source material solution, the retained activity of the daughter nuclides in the source material solution, and subsequent generation and accumulation. Thus, the software can calculate the estimated source activity. Furthermore, in some exemplary embodiments, the fluid transfer system 200 may include a dosimeter. Thus, the software can calculate the estimated source activity based on the tracked fraction of the eluted source material solution, the retained activity of the daughter nuclides in the source material solution, subsequent generation and accumulation, and the determined dose. As used herein, the term “production and accumulation” is defined as the continuous decay of the parent nuclide. Therefore, even after the daughter nuclide has leached from the parent nuclide, the parent continues to decay into the daughter nuclide. The software can be configured to track the concentrations of the parent and daughter nuclides over time and provide estimated yields from the leaching of the source at any given point in time.

[0053] As shown in Figure 3, in the third step, the source material solution is moved again from one or more transfer positions 420 to one or more source positions 410 in the source container. Therefore, in one exemplary embodiment of the third valve configuration, the orientation of the pump valve 232 can be adjusted to change the direction of flow through the fluid transfer system 200. Thus, the third step may be called a source return step or unloading step because the source material is returned to one or more source positions 410. In some embodiments, the source material is reflowed through column 310 either from top to bottom or bottom to top, depending on the orientation of the PSC valve 242. However, in other embodiments, the PSC valve 242 is positioned to bypass column 310. In another exemplary embodiment, the pump 220 may be designed to flow in the reverse direction to change the direction of flow through the fluid transfer system 200.

[0054] As shown in Figure 4, in the fourth step, the conditioning liquid is flowed through the entire column 310 to wash away any residual nuclides from the column 310. Therefore, the conditioning liquid may also be a washing solution. The conditioning liquid can be collected in the recycling container 510. Thus, similar to the first valve configuration, in an exemplary embodiment of the fourth valve configuration, the inlet valve 212, pump valve 232, PSC valve 242, and outlet valve 252 can be arranged so that the conditioning liquid enters the fluid transfer system 200 via the inlet manifold 210, passes through the pump 220, through the pump manifold 230 and the PSC manifold 240, through the column 310 of the PSC bay 300, through the PSC manifold 240 again, through the outlet manifold 250, and is discharged into the recycling container 510 of the recycling accumulator 500. In one preferred embodiment, the parent nuclide is Mo4 -2The source of the molybdenum is Mo99, and the conditioning solution is NaOH. Therefore, when column 310 is washed with the conditioning solution, the remaining molybdenum source material is washed away from column 310, but its daughter nuclide, Tc99m, is not washed away because it binds to column 310 when the pH value is high.

[0055] In the fifth step shown in Figure 5, the stripping solution is introduced into the elution system 100 through the second inlet 120 and flows through the entire column 310 to initiate a decrease in pH and flush out excess conditioning solution. The used stripping solution can be collected in the recycling container 510. Furthermore, in one exemplary embodiment, the flow through the column 310 can be reversed so that the stripping solution flows out from the bottom to the top of the column 310. Thus, the direction of the flow through the column 310 can be based on the loading direction of the supply source.

[0056] In a preferred embodiment, the stripping solution is a salt solution. To limit contamination within the elution system 100, the stripping solution can be pushed through the system using a stripping solution pump 122. Thus, the stripping solution does not pass through the pump 220. In an exemplary embodiment of the fifth valve configuration, the inlet valve 212, pump valve 232, PSC valve 242, and outlet valve 252 are arranged such that the stripping solution enters the fluid transfer system 200 via the inlet manifold 210, is directed away from the pump 220 through the pump manifold 230, enters the PSC manifold 240, passes through the column 310, passes through the PSC manifold 240 again, passes through the outlet manifold 250, and is discharged to the recycling container 510 of the recycling accumulator 500. As shown in Figure 6, after washing, column 310 can have a pH value low enough to release daughter nuclides. Thus, the product (i.e., daughter nuclides) can be collected in product container 620 of product bay 600.

[0057] In one exemplary embodiment of the sixth valve configuration, the inlet valve 212, pump valve 232, PSC valve 242, and outlet valve 252 are arranged such that the stripping solution enters the fluid transfer system 200 via the inlet manifold 210, is directed away from the pump 220 through the pump manifold 230, enters the PSC manifold 240, passes through the column 310, passes through the PSC manifold 240 again, passes through the outlet manifold 250, and is discharged to the product container 620. As discussed above, the product bay 600 may include a guard column 610 upstream of the product container 620. The guard column 610 may help filter out impurities from the product before collecting the product in the product container 620. Furthermore, in another exemplary embodiment, the flow through column 310 can be reversed, causing the stripping solution to flow out from the bottom to the top of column 310. Thus, the direction of the flow through column 310 may be based on the loading direction of the supply source.

[0058] In the seventh step, the conditioning fluid can be prepared for subsequent operation by flowing it back into the system. Thus, similar to the first and fourth valve configurations, in the seventh valve configuration, the inlet valve 212, pump valve 232, PSC valve 242, and outlet valve 252 are arranged such that the conditioning fluid enters the fluid transfer system 200 via the inlet manifold 210, is directed through the pump manifold 230 and pump 220, enters the PSC manifold 240, passes through the column 310 of the PSC bay 300, passes through the PSC manifold 240 again, passes through the outlet manifold 250, and is discharged to the recycling container 510 of the recycling accumulator 500.

[0059] As described above, the pump valve 232 and the PSC valve 242 can be arranged to accommodate multiple different flow paths. Therefore, the pump valve 232 can be a rotary reverse bypass valve. Thus, the pump valve 232 can be configured to allow forward flow through the pump 220 and the flow path connected to it, to allow reverse flow through the pump 220 and the flow path loop, or to bypass the pump 220 flow path loop. Furthermore, the PSC valve 242 can be a rotary reverse bypass valve. Thus, the PSC valve 242 can be configured to allow flow from top to bottom through the column 310, to flow from bottom to top through the column 310, or to bypass the column 310.

[0060] It should be understood that between each of the above fluid steps, air may be used to remove fluid from the fluid path of the elution system 100. It should be further understood that the elution system 100 may include one or more components typical of an elution system, although these are not described herein. Therefore, the above description and examples are intended to be illustrative and should not be construed as limiting. Furthermore, other modifications are possible within the spirit and scope of the invention and will be readily apparent to those skilled in the art.

Claims

1. A method for eluting an eluate containing a desired daughter nuclide with a desired concentration of radioactive activity, A step of contacting a separation particle with an aqueous solution containing a mixture of a parent nuclide and a desired daughter nuclide, wherein the desired daughter nuclide has a high affinity to the separation particle and binds to the separation particle, and the parent nuclide has a low affinity to the separation particle and does not bind to the separation particle, thereby forming a dispersion containing at least water, separation particles, the desired daughter nuclide, separation particles bound to the desired daughter nuclide, and unbound parent nuclide; A step of maintaining the contact for a sufficient time for the unbound desired daughter nuclide to bind to the separated particle; A step of separating the unbound parent nuclide from the separated particles bound to the desired daughter nuclide using a washing solution; A step of using a certain volume of stripping solution to strip a first fraction of a desired bound daughter nuclide from the separated particles to form an aqueous elution solution having the desired daughter nuclide activity; and Steps to retain the desired daughter nuclide of the second fraction in the separated particles. Methods that include...

2. The desired daughter nuclide is TcoO 4 -1 Tc99m or ReO 4 -1 The method according to claim 1, wherein Re188 exists as such.

3. The separated particles are a plurality of covalently bonded -X-(CH 2 CH 2 O) n -CH 2 CH 2 R group (In the formula, X is O, S, NH, or N-(CH 2 CH 2 O) m -R 3 Here, m is a number with an average value from zero to approximately 225, n is a number with an average value from approximately 15 to approximately 225, and R 3 is hydrogen, C 1 -C 2 Alkyl, 2-hydroxyethyl, or CH 2 CH 2 R is, and R is, - OH, molecular weight is -(CH 2 CH 2 O) n C, which has a molecular weight of up to approximately one-tenth of the portion. 1 -C 10 Hydrocarbyl ethers, carboxylates, sulfonates, phosphonates, and -NR 1 R 2 Selected from a group consisting of R 1 and R 2 Each of them independently contains hydrogen and C 2 -C 3 Hydroxyalkyl, or C 1 -C 6 Alkyl or -NR 1 R 2 Together, they form a 5- or 6-membered cyclic amine having zero or one oxygen atom, or zero or one additional nitrogen atom, within the ring. The separated particles include CH4, and the number of separated particles is greater than about 8,000 and less than about 1,000,000. 2 0 percent / particle surface area mm 2 The method according to claim 2, having the following characteristics.

4. The desired daughter nuclide Tc99m has a parent nuclide of Mo 4 -2 The method according to claim 2, which exists as such.

5. The desired daughter nuclide Re188 has a parent nuclide that is WO 4 -2 The method according to claim 2, which exists as such.

6. The desired daughter nuclide is Ac +3 The method according to claim 1, wherein Ac225 exists as such.

7. The desired daughter nuclide Ac225 has a parent nuclide of Ra +2 The method according to claim 6, which exists as such.

8. Ra +2 The method according to claim 6, wherein Ra225 and Ra226 are one or both of the above.

9. The separated particles are dispersed on a porous inert resin or silica support, and the structure is given by the following formula I: 【Chemistry 1】 (In the formula, R 1 , R 2 , R 3 , and R 4 They are either identical or different, and are a hydro or hydrocarbyl group, R 1 +R 2 +R 3 +R 4 The total number of carbon atoms is approximately 14 to 56. The method according to claim 6, comprising a diglycolamide extractant corresponding to the present invention.

10. The desired daughter nuclide is Ga +4 The method according to claim 1, wherein Ga68 exists as such.

11. Desired daughter nuclide Ga +4 The parent nuclide is Ge +4 The method according to claim 8, which exists as such.

12. The method according to claim 11, wherein the separated particles comprise a strongly basic anion exchange resin having quaternary ammonium functional groups bonded to a styrene-divinylbenzene copolymer lattice crosslinked with about 2 to about 12% by mass of divinylbenzene.

13. The desired daughter nuclide is Bi +3 The method according to claim 1, wherein Bi213 exists as such.

14. The parent nuclide of the desired daughter nuclide is Ac +3 The method according to claim 13, wherein Ac225 exists as such.

15. An elution system for eluting an eluate containing a desired daughter nuclide with a desired activity concentration of the nuclide, First inlet for conditioning liquid; Second inlet for stripping fluid; A fluid transfer system that is in fluid communication with the first and second inlets; A fluid transfer system and a primary separation cartridge (PSC) bay connected to the fluid; A fluid transfer system and a fluid-connected source container; and Fluid transfer system and fluid-connected product bay A dissolution system including

16. Fluid transfer system, An inlet manifold, comprising an inlet valve configured to direct the direction of fluid flow through the inlet manifold; A pump manifold located downstream of an inlet manifold and in fluid communication with the inlet manifold, including a pump valve configured to direct the direction of fluid flow through the pump manifold; A pump located downstream of the inlet manifold, with fluid communication to the pump manifold; A PSC manifold located downstream of a pump manifold and in fluid communication with the pump manifold, including a PSC valve configured to direct the direction of fluid flow through the PSC manifold; and An outlet manifold located downstream of the PSC manifold and in fluid communication with the PSC manifold, including an outlet valve configured to direct the direction of fluid flow through the outlet manifold. The elution system according to claim 15, including the following:

17. The elution system according to claim 15, wherein the PSC bay includes one or more isolation columns.

18. The elution system according to claim 15, wherein the supply source container includes one or more supply source locations and one or more transfer locations.

19. The elution system according to claim 15, further comprising a recycle accumulator, the recycle accumulator comprising one or more recycle containers designed to collect one or more fluids that have passed through the elution system.

20. The elution system according to claim 15, wherein the product bay includes a product container.

21. The elution system according to claim 15, wherein the product bay includes a guard column upstream of the product container.

22. The elution system according to claim 15, comprising a stripping solution pump located downstream of the second inlet, in fluid communication with the second inlet, and upstream of the fluid transfer system.

23. A method for improving the radionuclide activity of an aqueous eluate containing a desired daughter nuclide separated from an aqueous composition containing a parent nuclide and a daughter nuclide, comprising: 1) contacting the aqueous composition with a separation medium so that the desired daughter nuclide has a high affinity to the separation medium and binds to the separation medium, while the parent nuclide has a low affinity to the separation medium and does not bind to the separation medium, thereby forming a dispersion containing at least water, a separation medium, a desired daughter nuclide, a separation medium bound to the desired daughter nuclide, and an unbound parent nuclide; 2) maintaining the contact for a time sufficient for the unbound desired daughter nuclide to bind to the separation medium; 3) separating the unbound parent nuclide from the separation medium bound to the desired daughter nuclide formed in step 2) using a washing solution; 4) stripping the bound desired daughter nuclide from the separation medium using a certain volume of stripping solution to form an aqueous eluate; in the method, The improvement is a method comprising stripping a first fraction of a desired bound daughter nuclide from a separated particle using a certain volume of stripping solution to form an aqueous elution solution having the desired daughter nuclide activity, thereby retaining a second fraction of the desired daughter nuclide on the separated particle, thereby improving the desired daughter nuclide activity in subsequent elution compared to a method in which the separated particle does not retain a fraction of the desired daughter nuclide.

24. The desired daughter nuclide is TcoO 4 -1 Tc99m or ReO 4 -1 The method according to claim 23, wherein Re188 exists as such.

25. The desired daughter nuclide Tc99m has a parent nuclide of Mo 4 -2 The method according to claim 2, which exists as such.

26. The desired daughter nuclide Re188 has a parent nuclide that is WO 4 -2 The method according to claim 2, which exists as such.

27. The desired daughter nuclide is Ac +3 The method according to claim 1, wherein Ac225 exists as such.

28. The desired daughter nuclide Ac225 has a parent nuclide of Ra +2 The method according to claim 6, which exists as such.

29. Ra +2 The method according to claim 6, wherein Ra225 and Ra226 are one or both of the above.

30. The desired daughter nuclide is Ga +4 The method according to claim 1, wherein Ga68 exists as such.

31. Desired daughter nuclide Ga +4 The parent nuclide is Ge +4 The method according to claim 8, which exists as such.

32. The method according to claim 1, wherein the parent nuclide of the desired daughter nuclide Re186 is present in W186.

Images